Many therapeutics used to treat diseases, for example cancer, infectious diseases, inflammatory diseases, exhibit toxicity or confer undesirable side effects at doses that limit the amount of the therapeutic that can be safely administered and therefore limit the benefit provided by such therapeutics. It would be preferable if such drugs could be administered in a prodrug form that masked the inherent toxicity of the compounds from healthy tissues, and yet released the fully active drug species at the desired site of action. Such a technology would have the potential to increase the therapeutic window of a variety of drugs, possibly allowing them to be used safely at a more efficacious dose, and with reduced incidence of undesired side-effects for the patient. The use of prodrugs to confer improved properties such as increased bioavailability or aqueous solubility is a well established concept in the art of pharmaceutical research.
Matrix metalloproteinases (MMPs) are a ubiquitous class of zinc(II)-dependent hydrolytic enzymes that have been associated with a wide range of pathologies including cancer, arthritis, heart disease, and stroke.1-3 Clinical trials of matrix metalloproteinase inhibitors (MMPi) have frequently been hampered by the onset of musculoskeletal syndrome (MSS), which manifests as severe joint pain, and has been attributed to non-specific, systemic inhibition of MMPs and other metalloenzymes.4,5 
Provided herein are compositions and methods that address these and other problems in the art.